An increasing body of evidence is accumulating which indicates that some factor(s) related to the ingestion of food influences normal pituitary-adrenal hormone secretions, alters the periodicity of their circadian rhythms and interrupts their stress-induced secretory responses. The goal of this investigation is to define the role of the gastro-intestinal hormones, particularly those recently demonstrated to exist in brain tissues, in this gastrointestinal:pituitary-adrenal interaction. Proposed studies will involve both direct in vitro and indirect in vivo examination of the influence of GI hormones (gastrin, secretin, CCK, VIP and bombesin) on rat adrenal corticosterone, pituitary ACTH and hypothalamic stalk median eminence CRF secretion. In vitro studies will u tilize isolated adrenal cells, isolated pituitary cells (stagnant or cell column) and/or hypothalamic fragment preparations. The same techniques, and/or ACTH RIA, will be used to assay CRF and ACTH released into the blood during in vivo studies. corticosterone will be measured fluorometrically or by competitive protein binding assay. Observed in vitro responses will be characterized by altering the experimental conditions in two ways: 1) manipulation of the environment of the rats before use, i.e. fasted vs fed, morning vs. evening testing; 2) manipulation of in vitro assay conditions, i.e. presence of other known stimulants and inhibitors of pituitary-adrenal secretion. In vivo responses will be characterized by manipulation of the experimental conditions, i.e. route of hormone administration-peripheral vs. intraventricular, gasted vs. fed animals, morning vs. evening drug administration, etc. Data gathered from the proposed studies should significantly improve our understanding of the control of the hypothalamic-pituitary-adrenal neuroendocrine axis.